The project consists of a series of clinical trial evaluating the clinical efficacy and safety of experimental therapeutic agents for the control of acute pain and perioperative apprehension in ambulatory patients undergoing minor surgical procedures. The surgical removal of impacted third molars serves as a model for minor surgical procedures with associated intraoperative and postoperative pain and perioperative apprehension. All studies are double-blind with randomly allocated, parallel treatment groups and multiple dependent measures of therapeutic efficacy and clinical safety. A continuing study is evaluating the analgesic efficacy of two antihistamine drugs in comparison to ibuprofen and placebo. Terfenadine, a H1 histamine receptor blocker, and ranitidine, a H2 histamine receptor blocker, are administered one hour prior to oral surgery and the onset and severity of postoperative pain monitored for four hours postoperatively. Preliminary results suggest that both antihistamine drugs are exerting an analgesic effect which is greater than placebo but less than the effects of ibuprofen 400 mg. Successful demonstration of an analgesic effect for the antihistamine drug class will provide a rationale for a factorial study to evaluate the combination of an antihistamine and ibuprofen. Drugs acting through separate mechanisms should result in additive analgesia and the lack of central effects for these two drug classes should provide a therapeutic advantage without increased side effects for these two drug classes should provide a therapeutic advantage without increased side effects in ambulatory patients. A second study evaluated the analgesic potential of a drug acting at the receptor site for prostaglandin E2 to block the sequelae of the inflammatory process mediated by prostaglandins. Comparison was made to 1000 mg of acetaminophen and placebo, with all treatments being administered one hour prior to oral surgery. Preliminary results did not demonstrate any effect of the prostaglandin receptor antagonist to suppress pain in comparison to either acetaminophen or placebo. This finding suggests that the dose of the drug evaluated was too low or that blockade of the prostaglandin E2 receptor is not a useful strategy for analgesia in the oral surgery model of acute pain.